The overall goal of this submission is to improve disease prevention and improve barrier housing in the large animal vivarium in the Ryan Veterinary Hospital of the University of Pennsylvania (VHUP) of the School of Veterinary Medicine (SVM). Funding is requested to replace the old, frequently inoperable, and inadequately sanitizing cage washer for the dog and cat colonies; to isolate the experimental surgery suite from nosocomial infections and control exposure to BSL-2 agents; and to correct deficiencies in the housing spaces for immunologically deficient animals and other models. This renovation will directly benefit at least 15 investigators with more than $5 million in annual direct support to conduct biomedical research on cat and dog disease models. The major research user group is the cross-departmental, inter-disciplinary Center for Comparative Medical Genetics (CCMG). The CCMG investigators maintain more than 25 independent breeding colonies of dog and cat models of human genetic diseases. This is the largest collection of such models in the world, and many of these valuable mutations do not exist anywhere else. The types of inherited diseases include cardiac abnormalities, inborn errors of metabolism, immune deficiencies, skin disorders, retinal degeneration diseases, and hematologic disorders. Studies utilizing these animals include mode of inheritance, mutation analysis, mechanisms of pathogenesis, gene therapy, stem cell transplantation, and other basic and translational research areas. The vivarium is also used by other investigators in the SVM who have NIH-funded research for dogs and cats in parasitology, pain, sepsis, cancer, and other disorders. The vivarium urgently needs upgrading to insure that these rare and fragile disease breeding colonies are protected from animal diseases and that modern A-BSL-2 experiments can be conducted with protection for both the animals and the scientific and vivarium staff.